Nutrient ration for increasing growth of livestock and poultry

ABSTRACT

A method of increasing the rate of growth of livestock and poultry which comprises feeding said livestock or poultry a nutrient ration containing a small amount of 5&#39;&#39;-nucleotide, preferably one of the 5&#39;&#39;-monophosphates of cytidine, adenosine, quanosine or uridine or mixtures thereof. The ration can be a synthetic milk or a grain feed or forage.

United States Patent [151 3,686,392 Hamada et a1. [4 Aug. 22, 1972 [54] NUTRIENT RATION FOR INCREASING 2,921,853 l/1960 Card et a1. ..99/ 140 X GROWTH OF LIVESTOCK AND 2,932,571 4/ 1960 Tribble et a1. ..99/2 POULTRY 3,104,171 9/ 1963 Sakaguchi et a1 ..99/140 N [72] Inventors: Yoshio Ramada Tokyo; Motohisa 3,362,828 1/1968 Thrasher et al ..99/2

Y0shm1 Sum, 1 Japan FOREIGN PATENTS OR APPLICATIONS [731 Assigneei Takeda Chemical Industries, Ltd-a 1,394,330 4/1965 France ..99 2

Osaka, Japan 22 Filed: Jan. 26, 1966 OTHER PUBLICATIONS Chemical Abstracts (11) Vol. 55 (1960) page 10735. Forelgn pp Priority Data Chemical Abstracts 111 V0]. 52 (1958) page 7481.

J .27, 1965 J ..-,....45 4 63 6. 3, 1965 135:: "40/61 196 shaplm Att0rney-Wenderoth, Lind & Ponack [52] US. Cl ..424/16, 99/2 G, 424/180,

- 99/4 57 ABSTRACT [51] Int. Cl. ..A23k 1/00 A method of increasing the rate of growth of livestock [58] F'eld of Search "99/140 2 9; and poultry which comprises feeding said livestock or 195/28 N poultry a nutrient ration containing a small amount of 5-nuc1eotide, preferably one of the 5- [56] References and monophosphates of cytidine, adenosine, quanosine or UNITED STATES PATENTS uridine or mixtures thereof. The ration can be a synthetic milk or a grain feed or forage. 3,168,446 2/1965 Omura et a1 195/28 2,703,285 3/1955 Luther ..99/7 10 Claims, No Drawings NUTRIENT RATION FOR INCREASING GROWTH OF LIVESTOCK AND POULTRY This invention relates to a feeding composition for livestock and poultry, and more particularly it relates to a feeding composition containing 5 '-nucleotide such as I cytidine 5'-monophosphate,' adenosine 5'- monophosphate, guanosine 5 '-monophosphate, uridine 5-monophosphate or inosine 5 '-monophosphate (each of these 5'-nucleotides is hereinafter referred to as 5'- CMP 5 I AMP,, 5 I GMP,, G5 I UWQQ SI 1MP, respectively) or salt thereof.

One trend in modern nutrition is toward the rapid production of marketable livestock or poultry. Another trend is toward the improvement of the feed efficiency or feed conversion from feed to weight of livestock or p t y- It has now been, discovered that the inclusion of small amounts of 5'-nucleotide in livestock or poultry feeds increases the rate of growth of the livestock or poultry and improves the feed efficiency or feed conversion from feed to weight of livestock or poultry; in most instances the desirability of the feed composition containing 5 -nucleotide increases the degree of acceptance of the feed. Further, it has been discovered that the feed composition: synthetic'milk containing 5 nucleotide, can be used as a remarkable milk replacer for suckling livestock. And it has also been discovered that these milk replacers never cause such undesirable effects as loose bowels or other diseases observed in the feeding of known milk replacers.

As 5'-nucleotide in the present invention, there may be used, for example, 5'-CMP, 5'-AMP, 5'-UMP, 5'-

'GMP or 5'-IMP or their alkali metal (e.g. sodium,

potassium, etc.) or alkaline earth metal (e.g. calcium, etc.) salt. These compounds can be prepared by per se known methods such as enzymatic means, chemical synthesis or hydrolysis of nucleic acid which can be extracted from living tissues e. g. microorganisms, animal tissues, etc.), and may be used independently of or combinatively with each other, or may be fed in combination with glutamic acid, sodium glutamate or others. Generally, the amount of 5'-nucleotide added will fall in the range of from 0.001 to '1 percent by weight based on the total weight of the feed composition though it may vary with the difference of the 5- nucleotide used, the livestock and poultry fed, or the stage of feeding. The desirable amount added to a milk replacer is as follows, for example:

5 '-nucleotide Calf Colostrum milk Colostrum milk by wt.) bywt.) by wt.) by wt.)

5-AMP 0.002-0.005 0.0050.0l0.00l0.005 -0.004 '-GMP 0.01 0.03 0.01 0.03 0.001-0.002 0.001-0.002 5'-UMP 0.05 0.3 0.03 0.3 0.005-0.l5 5'-CMI 0.0050.03 0.001-0.003

soybean meal, cottonseed meal, and linseed meal; forage, both greenvand dry, e.g. legumes and grasses such as for instance alfalfa and clover; and by-products of sugar manufacture, molasses, beet pulp and the like. Mixtures of two or more of these feed ingredients can be present in such combinations as will fulfil the nutrient requirement of the animal. These feeds may contain other sources of protein, fat, minerals and vitamins. I

The additive can be incorporated in the feeds in any convenient manner. However, as 5 '-nucleotide is easily destroyed by phosphatase which is contained in most feeds, the phosphatase should be inactivated or destroyed just after or simultaneously with or before the addition of nucleotide fractions to sustain the effect of 5'-nucleotide. Though the inactivation or destruction of phosphatase may be effected by the addition of a phosphatase-inhibitor (e.g. arsenates, phosphates or cyanates), most of these are unsuitable as additive to feed for livestock or poultry, and therefore use of a phosphatase-inhibitor is desirably avoided. The inactivation is preferably effected by heating for a short time, for example at 60 C for 40 minutes, at 65 C for 20 minutes, at C for 5 minutes, at C for 4 seconds or at C for only 1 second in the case of milk-type feed. Such a short heating does not at all affect the natural flavor or taste of the original feeds, but also there is no fear of contamination of unfavorable substance in the product.

As another method for protecting 5 '-nucleotide from decomposition with phosphatase, there may be employed expedients such as coating the 5'-nucleotide with a coating agent which is soluble in water, e.g. polyvinyl alcohol and polyethylene glycol, or another kind of coating agent which is not decomposed in the presence of water at room temperature but is decomposed at an elevated temperature. As the latter coating agent there may, for example, be employed wax (e.g. ozokerite, ceresin, utah wax or montan wax, paraffin wax, petrolaturn wax, carnauba wax, Japan wax, bayberry wax, flax wax, spermaceti, beeswax, chinese wax, shellac wax, etc.), an ester of a fatty acid having from 12 to 31 carbon atoms and a fatty alcohol having from 12 to 31 carbon atoms (e.g. myricyl palmitate, cetyl palmitate, cyricyl cerotate, cetyl myristate, ceryl palmitate, ceryl cerotate, cyricyl melissate, stearyl palmitate, stearyl myristate, lauryl laurate, etc.), fatty acids having from 10 to 22 carbon atoms (e.g. decenoic, docosanoic, stearic, palmitic, lauric, myristic acid, etc.), fatty alcohols having from 14 to 31 carbon atoms (e.g. lauryl, cetyl, stearyl, myristyl, myricyl, arachyl, carnaubyl, ceryl alcohol, etc.), the mono-, di-or triglyceryl esters formed from fatty acids having from 10 to 22 carbon atoms and the like.

The following examples further illustrate the invention but it is not intended that they limit the invention to the procedures, amount of active ingredient or described rations; but rather it is intended that all equivalents obvious to those skilled in the art be included within the scope of the invention. In this specification and claims, percentages are all on the weight basis, and in the examples, kg, g, mg, IU, 5'- UMP-Na," 5'-CMP-Na, 5'-AMP-Na, 5'-IMP- Na and 5'-GMP-Na stand for kilogram," gram," milligram," lntemational Units," disodium salt of 3 4 5'-UMP, disodium salt of 5'-CMP, disodium salt g p yyyyof 5'-AMP, disodium salt of S'JNIP and disodium salt of 5-GMP, respectively, and temperatures are all Control 14.44 18.47 19.19 14.80 uncorrected Test 16.02 22.55 23.93 18.20

5 TEST 1 Test animal, (3) Average feed consumed(kg) age of pigs One-htter size (8 heads) of Central Yorksh1re pigs, 60-90 90-120 120-150 150-180 which were divided equally in number into two 1 day'dd day'dd groups and tested. 10 Tesipeflod= v- 23-22 as; 22 21 22-22 From 60 day-old (at weaning) to 180 day-old. Feed used: I

Control group: Commercial concentration. 4 F d Test group: Commercial concentration 99.99 cc age of pigs I parts. A mixture of 5'-IMP-Na and 5'-GMP-Na 60-90 90-120 120-150 150-180 1.1 0 01 parts group day-old day-old day-old day-old l Control 3.35 3.22 v 4.30 5.43 Composltlongiagfommerclal Concentration. 27% v Test 3'1 5 3'13 390 4.85

rice bran 10% com 28% barley 15% alfalfa meal 5% 5. Others :91; bean meal Z: The pigs of the control group had loose bowels after z 'fiz 15% several days from the start of test, while in the test sodium chloride 0.5% group no such symptom was found.

mineral mixture* 0.1% vitamin mixture" 0.15% TES antibiotic feed supplement 0.05% T 2 calcium secondary phosphate 0.5% Test animal:

30 6 suckling Yorkshire pigs, which were divided 2 2522;? 24% equally in number into two groups and tested.

i 1 Test period: i: From 5 day-old to 60 day-old. pp iodine 0.5% 3 5 Feed cobalt 0.2% vitamin mixture contains: period 3 383388 s49 day-old 20-26 day-old 27-60 day-old vitamin E 400 w 5MP vitamin B,, 1.6 mg 2522 5 40 Control colostrum milk A milk B milk A if 3 333 :2 Test colostrum milk A milk B menadione 264 mg mflk A dl-methionine 68 mg folic acid 60 mg l ,2-dihydro-6-ethoxy- 2,2,4-trimethyl-quinoline 1.4 mg milk A(%) mllk B(%) Commercially available as Aurofac-lO (American Cyanamid Co.) which is a feed supplement or premix containing, per wheat flout 553 25-97 pound of premix, 10.0 grams of soybean Aureomycin and chlortetracycline (treated at 120C) 20 0 hydrochloride. yellow com 0 35 Result: (1) Weight gain milk A(%) milk B(%) Average body weight per pig(kg) age of pigs day-old dayold day-old 55 soybean powder 0 5 group (at starting) (raw) fish meal 8.44 6.3 for 0 3.5 Control 14.20 28.64 47.1 1 ig 133 12 13-94 29-96 52-31 calcium carbonate 1.25 1.2 calcium secondary phosphate 0.2 0.2 6 mineral mixture 0.05 0.05 yysodium chloride 0.5 0.5

Aurofac-lO 0.2 0.12v C t I 66 20 81 00 vitamin mixture 0.16 0.16

rotease 0.1 0 Test 76.24 95.48 p

(2) A (k 2",""eachisthesameasinTestl.

verage gain g age of pi 60-90 90-120 120450 150-1 so milk A:

Commercial synthetic milk containing higher than 25 percent of crude protein, higher than 5 percent of crude fat, higher than 3 percent of crude fiber and higher than 7 percent of crude ash.

milk B:

Commercial synthetic milk containing higher than 21 percent of crude protein, higher than 3 percent of crude fat, higher than 3'percent of crude fiber and higher than 7 percent of crude ash.

milk A: 10

Synthetic milk consisting of 99.99 percent of milk A and 0.01 percent of an equivalent mixture of 5-IMP-Na, 5'-GMP-Na, 5'-CMP-Na and 5'- UMP-Na. v

milk B: I

Synthetic milk consisting of 99.99 percent of milk B and 0.01 percent of an equivalent mixture of 5 '-lMP-Na, 5 -GMP-Na and 5'-CMP-Na and 5 UMP-Na. r v

Result: (1) Average body weight per pig(kg) age of pigs 5 day-old 20 day-old 60 day-old group Control 1.63 2.52 8.1 Test 1.62 2.83 60.7

(2) Weight gain (5-60 days) I group average gain average synthetic average feed per pig(kg) milk consumedflrg) conversion Control 6.46 13.24 2.05 Test 9.08 15.61 1.73

TEST 3 Test animal:

9 suckling Central Yorkshire pigs, which were divided equally in number into three groups and tested. Test period:

From 22 day-old to 60 day-old pigs. Feed used:

age of pigs 1-2 3-10 1 1-22 23-26 27-60 group days days days days days Control 1 colostcolostrum milk A milk A milk B rum milk A Control 2 colostcolostrum milk A milk A milk B rurn milk A cow's milk Test colostcolostrum milk A milk A milk B rum milk A milk A, A, B and B are the same as in Test 2.

Result:

Control 1 Control 2 Test Average initial weight( kg) 1.47 1.35 1.35 Average weight at 22 dayo1d(kg) 3.8 4.2 4.8 Average final weight(kg) 13.1 14.4 16.7 Average gain per pig in the 9.3 10.2 1 1.9 period of 22-60 dayold(kg) Average Feed conversion 1.99 1.83 1.81

TEST 4 Test animal:

10 calves, which were divided equally in number,

into two groups and tested. Test period:

From 2 to 22 week-old calves. Feed used:

8 1 Test (glcalf/day) Control age milk calf-starter starter roughage of calves replacer (hay) l-4 day-old colostrum 5-7 500 8-10 750. a little a little 1 1-20 1000 a little a little Total 21-30 1000 200 200 mother's milk 280kg/calf 31-35 750 600 300 det'at milk 600kg/calf 36-40 500 1000 400 starter 41-45 250 1300 500 l24kg/calf 46-55 1500 700 56-80 1700 1000 81-100 2000 1500 101-110" 1000 1000 2000 11 1-150 2000 2500 Total 3 1 124 (kg/calf) After day-old starter 2000g/calf/ day hay 3000g/calf/day.

milk replacer:

det'at milk 70% whey 5% 5 '-nucleotide mixtures 10% glucose 6.5% lard 5% mineral mixtures 0.5% vitamin mixtures 3% TDN (Total Digestible Nutrions) 88. 15% CP (Crude Protein) 27.25% DCP (Digestible Crude Protein) 25.65%

calf-starter:

soybean oil meal 15% linseed meal 10% com 20% cats 20% forage 20% 5'-nucleotide mixtures 10% molasses 2% mineral mixtures 0.5% vitamin mixtures'" 2.5%

TDN 69.18% CP 20.54% DCP 17.46%

*5'-nuc1eot1de mixtures contains 0.15% of 5-CMP-Na, 0.03% of 5'- AMP-Na, 0.26% of 5 '-UMP-Na, 0.05% of 5'-1MP-Na, and 0.09% of 5'- GMP-Na.

"mineral mixtures contains 24% of manganese, 18% of zinc, 8% of ifron, 1% of copper, 0.5% of iodine and 0.2% of cobalt in available orm.

Result:

Average body weight per/calf(kg) age of calf 16 week-old 22 week-old group .7. Control 1 13 125 Test 123 147 TEST Test animal:

Hiiku No. 1 (chicken for broiler) Test period:

-From 1 to 60 day-old. Number of one group:

female 30 male 30 Feed used:

Group Feed used l basal diet 99.95% 5'-1MP-Na 0.05 2 I 5-GMP-Na 5"AMP-Na Control Composition of basal diet yellow com 45% rice bran 4% forage 4% soybean meal 9% fish meal 6% fish soluble 3% alfalfa meal 2% calcium carbonate 5% calcium tertiary phosphate 0.4% sodium chloride 0.35% vitamin mixture 0.1% mineral mixture 0.05% Furazolidone 0.01%

,"t each is the same as in Test 1.

Result:

initial final No. of averageNo. of average average average group chickwt. perchickweight feed feed ens chickerens per consumed con- (g) chicken (g) version l 60 74 59 1,305 3,898 3.1 2 60 75 58 1,272 3,738 3.1 3 60 74 59 1,340 3,888 3.0 Con- 60 75 55 1,317 4,183 3.3 trol TEST 6 Test animal:

White leghom (chicken breeder) Test period:

From 1 to 30 day-old chicken Result:

age group control 1 2 initial average weight 33 33 33 per chicken(g) average weight 100 98 95 per chicken(g) 10-day-old Total feed used 1 88 1 20 1 14 per chicken( g) average feed 2.8 1.7 1.7 conversion 20 day-old average weight 216 208 208 per chicken(g) total feed used 560 440 440 per chicken(g) average feed 3.0 2.5 2.5 conversion 30 day-old average weight 364 356 352 per chicken( g) total feed used 1 100 800 860 per chicken(g) average feed 3.3 2.7 2.6 I conversion 40 day-old average weight 548 540 520 per chicken(g) total feed used 1740 1430 1439 per chicken( g) average feed 3.3 2.8 2.9

conversion Following are illustrative examples of presentlypreferred compositions according to the invention. It will be understood that the compositions proper are widely variable. Any conventional livestock or poultry feed, especially those recommended by the American Nutrition Research Council, may be employed as basal diet to be improved according to and for the purposes of the present invention.

Example 1 Chick pre-starter composition Number of one group: Phosphate containing from 26 to 32% calcium and 18% phosphorus. male 25 Any conventional poultry feed flavor (e.g., Peckmor, sold by Flavor Feed used; Corporation of America).

Example 2 group Feed used Chick starter composition Ingredients: g Control basal diet 1 99.5% 5'-nucleotide mixtures 0.5% ml? 283 u I it 2 99% 5 -nucleot|de mixture 1% Soybean il al (44%) 560 Alfalfa meal 60 Dried whey 50 Fish meal (60%) 50 the same as in Test 5. Phosphate 30 "5-nucleotide mixtures containing 0.15% of 5'-CMP-Na, 0.03% of Salt 10 5-AMP-Na, 0.26% of 5'-UMP-Na, 0.05% of 5'-lMP-Na and 0.09% of Manganese sulfate 0.5 5'-GMP-Na. Poultry feed flavor" 0.5

9 l '-lMP-Na 01 Exam 5'-GMP-Na 0.l Plc 6 Pig pre-starter composition Ingredients: g

*,the same as in Example 1 5 Ground yellow corn 435 Sucrose 200 Example 3 Dried skim milk 600 Fish meal (60%) 100 a i Soybean oil meal 44% 400 E Dried whey 100 10 Condensed fish solubles 40 Com 1050 zlasphate Soybean ml meal (50%) 625 Ground oyster shell or limestone l0 Alfalfa meal 50 Salt, iodiud 10 P l-m 'fq meal 50 Manganese sulfate 0.25 Drled whey 50 5'-CMP-Na s '-UMP-Na 0.1 phosPhate Sodium glutamate 1 Ground oyster shell or limestone Manganese sulfate 0.5 Poultry feed flavor 0.5

gigfl gz "the same as in Example 1 Example 7 the same as in Example 1 Sow feed composition Ingredients: g

Example 4 25 Corn 1340 Broiler finisher composition Wheat middlings 300' Ingredients: 3 Soybean oil meal (44%) 200 1 Tankage 60 Alfalfa meal 60 Corn 700 Phosphate 10, Wheat 600 30 Groundoyster shell or limestone 20 Soybean oil meal (50%) 320 I Salt 10 Poultry by-product meal 100 Manganese sulfate 0.25 Distillers dried solubles 50 5-lMP-Na 0.05 Condensed fish solubles 50 005 Alfalfa meal 60 ggg r Fat 50 mm g utamate Phosphate 30 3 5 Ground oyster shell or limestone 30 Salt l0 Manganese sulfate 0.5 the same as in Example 1 Poultry feed flavor" 0.5

5"lMP-N8 0.l Exam le 8 5 '-GM P-Na 0.1 p

Calf starter compositions Ingredients: g

,the same as in Example 1 Corn 560 Wheat middlings 400 Example 5 45 Soybean oil meal (44%) 400 Linseed meal 300 8 Mllk Replace! composltlons Distillers dried solubles so Alfalfa meal I00 Ingredients Starter Pre- Condensed fish solubles (g) starter Molasses l00 (g) Ground oyster shell or limestone 30 50 Salt l0 Manganese sulfate 0.25 Corn powder 30 30 Sodium glutamate 0.5 Wheat powder 28 23 5-nucleotide mixtures 3 Soybean powder (treated at 120C) 25 20 Fish meal 8 5 Molasses 4.5 g i mixtures the same as in Example 5 a Precipitated Calcium carbonate 0.4 0.45 Calcium secondary phosphate 0.6 0.7 Example 9 Aurofac-IO 0.2 0.3 H d f d pepsin 0.] OJ orsedan r nu e ee composltlon Spice for pig 0.05 0.05 8 Vitamin B,,(2.2%) 0.05 0.1 Sodium cyclohexylsulfamate 0.09 0.1 C

om (Cracked) 700 glen-fat mllk powder 2; Cats (Crimped) 800 Linseed meal 100 Alfalfa meal l00 Wheat bran 200 Molasses I00 '5'-nucleotide mixtures containing 015% of 5'-CMP-Na, 0.03% of 5'- Manganese sulfate 0.25 AMP-Na, 0.26% of 5'-UMP-Na, 0.05% of 5'-lMP-Na and 0.09% of 5'- 5'-nucleotide mixtures 3 GMP-Na. Sodium glutamate 1 "(see Note under Test 1, supra) "the same as in Example 1 Example Duck grower composition ingredients: g

Corn 500 Wheat 764 Soybean oil meal (44%) 60 Alfalfa meal 50 Wheat middlings 200 Fish meal (60%) 50 Meat and bone scraps (50%) 100 Oats, pulverized 10 Delactosed whey 10 Ground oyster shell or limestone 40 Salt 5.5 Manganese sulfate shell or limestone 0.5 5'-nucleotide mixtures 5 Sodium glutamate 2 "the same as in Example 1 I What is claimed is:

1. A method of increasing the rate of growth of livestock and poultry which comprises feeding said livestock or poultry a nutrient ration containing 0.001 to 1 percent by weight of 5 '-nucleotide.

2. A method as claimed in claim 1, wherein the 5- nucleotide is selected from the group consisting of cytidine 5 -monophosphate, adenosine 5 monophosphate, guanosine 5 '-monophosphate, uridine 5'-monophosphate and alkali metal salts and alkaline earth metal salts thereof.

3. A process as claimed in claim 1, wherein the livestock is suckling livestock.

4. A process as claimed in claim 2, wherein the livestock is suckling livestock.

5. A process as claimed in claim 1, wherein the 5'- nucleotide is guanosine 5 '-monophosphate.

6. A process as claimed in claim 1, wherein the 5- nucleotide is inosine 5 -monophosphate.

7. A process as claimed in claim 1, wherein the 5'- nucleotide is alkaline salt of guanosine 5'- monophosphate.

8. A process as claimed in claim 1, wherein the 5'- nucleotide is alkaline salt of inosine 5- monophosphate.

9. The method of claim 1 wherein the bulk of the nutrient ration is grain.

10. A solid feed composition for livestock and poultry comprising 0.001 to 1 percent of 5'-nucleotide by weight, the bulk thereof being grain, wherein the nucleotide is coated with a coating protecting it from decomposition by phosphotase. 

2. A method as claimed in claim 1, wherein the 5''-nucleotide is selected from the group consisting of cytidine 5''-monophosphate, adenosine 5''-monophosphate, guanosine 5''-monophosphate, uridine 5''-monophosphate and alkali metal salts and alkaline earth metal salts thereof.
 3. A process as claimed in claim 1, wherein the livestock is suckling livestock.
 4. A process as claimed in claim 2, wherein the livestock is suckling livestock.
 5. A process as claimed in claim 1, wherein the 5''-nucleotide is guanosine 5''-monophosphate.
 6. A process as claimed in claim 1, wherein the 5''-nucleotide is inosine 5''-monophosphate.
 7. A process as claimed in claim 1, wherein the 5''-nucleotide is alkaline salt of guanosine 5''-monophosphate.
 8. A process as claimed in claim 1, wherein the 5''-nucleotide is alkaline salt of inosine 5''-monophosphate.
 9. The method of claim 1 wherein the bulk of the nutrient ration is grain.
 10. A solid feed composition for livestock and poultry comprising 0.001 to 1 percent of 5''-nucleotide by weight, the bulk thereof being grain, wherein the nucleotide is coated with a coating protecting it from decomposition by phosphotase. 